基于多中心多模态磁共振影像的阿尔茨海默病及高危人群的情景记忆脑网络表征研究

Episodic memory is the memory of autobiographical events (times, places, associated emotions, and other contextual who, what, when, where, why knowledge) that can be explicitly stated. It is the collection of past personal experiences that occurred at a particular time and place. Alzheimer’s disease (AD) is a common progressive neurodegenerative disease that seriously affects human health. Converging pieces of evidence have suggested that the structural/functional alterations emerge more than 10 years before the onset of cognitive impairment. Mild cognitive impairment (MCI), especially amnestic MCI (aMCI), has been considered the prodromal stage of dementia and has a high risk of converting to AD. .Impaired performance of episodic memory is one of the first cognitive functions impaired and one of the core features of a diagnosis of AD. Episodic memory requires the medial temporal lobe, a structure including the hippocampus parahippocampus,entorhinal cortex and perirhinal cortex etc., which is also a region with the earliest neuropathologic changes associated with AD. .The main aim of the present project is to identify brain regions characterizing episodic memory network, to investigate the impaired pattern of episodic memory network in aMCI and AD based on multi-center and multi-modal MRI．For this purpose, we will focus on the following three aspects: 1) the elucidation of the key brain regions characterizing episodic memory network; 2) the manifestation of episodic memory network in normal subjects; 3) the characterization of impaired episodic memory network architecture in aMCI and AD patients..Studying impaired patterns of episodic memory network from the perspective of network will benefit for finding potential biomarkers or predictors of AD progression. This profile will provide new insights into AD pathophysiology, which is critical to better understand the neural basis of AD.

情景记忆即以时间和空间为坐标对个人亲身经历的、发生在一定时间和地点的事件的记忆。阿尔茨海默病(AD)是最典型痴呆之一，其患病人群认知功能严重受损，给社会带来了极大的经济负担。遗忘型轻度认知障碍 (aMCI)是AD的高危人群。情景记忆损害是aMCI/AD的核心认知症状之一，内侧颞叶（海马、内嗅皮层、嗅周皮层、旁海马皮质等）是情景记忆的重要区域，和AD的病理变化区有较高重合。主要目标：基于多中心、多模态磁共振影像，明确情景记忆的脑网络表征，揭示aMCI情景记忆脑网络异常表征。主要研究内容：1)情景记忆网络的核心脑区确定；2)情景记忆网络在正常人的表征；3)多中心研究情景记忆网络在正常人-aMCI-AD的变化模式、aMCI 的情景记忆脑网络纵向变化模式。研究意义：从网络水平上研究aMCI、AD的情景记忆脑网络异常，将有助于更加全面认识AD的病理基础，探寻早期识别影像学标记，具有重要的临床意义。

项目的总体目标就是利用多中心、多模态磁共振，明确情景记忆脑网络及在正常人中的连接模式和网络拓扑结构表征; 通过横向和纵向的对比，明确AD和高风险人群aMCI情景记忆的脑网络异常表征。主要研究内容包括：采取数据挖掘再分析和多模态数据综合分析的方法确定情景记忆脑网络的区域；然后基于多个中心、多模态的磁共振影像数据研究情景记忆脑网络的连接模式、情景记忆脑网络在aMCI、AD中的异常表征，探索网络异常表征和行为学之间的关系，异常表征的纵向变化特征。. 在项目支持下，研究团队建立了一个多中心多模态AD及高危人群的影像学数据库，入库数据超过3000例。项目组明确了情景记忆脑网络的区域及在AD及高危人群中的异常模式，利用多中心多模态影像研究了情景记忆网络的核心脑区的结构、功能和形态异常模式及与认知损害的生物学基础之间的关系。在Science Bulletin, Journal of Alzheimer Disease, Cortex等期刊上发表研究论文14篇，在SPIE medical Image, ISBI, EMBC等会议上发表论文5篇(其中Oral 2个)。申请专利和软件著作权5项，开源Brainnetome fMRI Toolkit (http//:brant.brainnetome.org)软件平台,目前已有13篇国内外同行的论文使用该软件平台，有力的促进了脑网络及临床应用研究。